tbuckley/cabot-search huggingface dataset:
Optical genome mapping for structural variation analysis in hematologic malignancies
Authors: Adam C. Smith, Kornelia Neveling, Rashmi Kanagal‐Shamanna
Journal: American Journal of Hematology (2022)

Optical genome mapping (OGM) is a technology that is rapidly being adopted in clinical genetics laboratories for its ability to detect structural variation (e.g., translocations, inversions, deletions, duplications, etc.) and replace several concurrent standard of care techniques (karyotype, fluorescence in situ hybridization, and chromosomal microarray). OGM can dramatically simplify lab workflow by reducing multiple tests (conventional karyotype, fluorescence in situ hybridization [FISH], and chromosomal microarray) into one test. The superior ability to detect structural variation across the genome removes the need for reflex FISH studies, which can dramatically reduce cost and turnaround time per sample. Parallel studies of OGM versus standard of care testing have demonstrated it can detect and resolve more abnormalities than karyotyping or FISH. However, like many molecular tests that normalize copy number it can have difficulty with non-diploid karyotypes. This Test of the Month review will summarize how the technique works, review the strengths and weaknesses of OGM compared to standard of care techniques and illustrate how the technique is likely to change front line testing in many hematologic malignancies-including summarizing the clinical utility in acute myeloid leukemia, myelodysplastic syndromes, and B cell acute lymphoblastic leukemia.
Underwater colonic endoscopic ultrasonography-guided fine-needle biopsy of a hypogastric neoplastic lesion
Authors: Benedetto Mangiavillano, Laura Lamonaca, Francesco Auriemma, Danilo Paduano, Federica Spatola, Alessandro Repici
Journal: Endoscopy (2022)

An 86-year-old woman was admitted to our endoscopy unit, having been referred by the oncologists. She had undergone a computed tomography scan because of weight loss and abdominal pain, and had been found to have a 6-cm hypogastric mass with contrast enhancement ([Fig. 1]). Her case was discussed by our multidisciplinary team and endoscopic ultrasonography (EUS) plus fine-needle biopsy (FNB) was proposed. Before performing EUS, we decided to perform an underwater colonoscopy, using a standard colonoscope and filling the bowel with tap water, to prepare the bowel for the water-filled technique. After colonic irrigation had been performed, an echoendoscope was advanced using the water-filled technique [1] and EUS guidance until the splenic flexure was reached, and the examination was performed by withdrawing the scope with rotational movement until the mass was visualized from the mid-sigmoid colon ([Video 1]). After visualization of the mass, an FNB was performed with two passes of a 22G needle (Acquire; Boston Scientific; Natick, Massachusetts, USA) and macroscopic on-site evaluation (MOSE) [2]. Histology revealed a gastrointestinal stromal tumor (GIST) and the patient was referred to the surgeons for further management.
Association of the Liver Acuity Circle Allocation Policy With Timing of Donor Procurements in the US
Authors: Ramya Radhakrishnan, Darius E. Chyou, David Seth Goldberg
Journal: JAMA Surgery (2022)

By 2017, there was no significant difference between private or government insurance and self-pay.Geographic disparities in GAS access diminished during the study period.Early predominance of cases in the West may be associated with state policies favorable toward GAS coverage.California was the first state to broadly expand Medicaid coverage for GAC in 2013 and had policies against discrimination in private insurance coverage. 1,4During the study period, Medicaid coverage for GAS was introduced in 12 states and state private insurance laws became more inclusive. 1,3,5his study is limited by reliance on ICD-9 and ICD-10 diagnosis and procedure codes, which may not represent the full range of GAS.GAS is often the final step in transition with the most stringent insurance preauthorization requirements, limiting generalizability of our results to other forms of GAC.Despite recent improvements, access to GAS remains limited.Less than half of state Medicaid programs provide for GAC, and in 2020, only 18% of the 3 largest private health plans by state had policies favorable for facial feminization surgeries. 1,
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Authors: Julie Reimann, Sean Moynihan, Thomas Horn, Dermatopathology Mgpo, Massachusetts Newton
Journal: JAMA Dermatology (2022)

Regarding concern for the impracticality of customizing DIF panels based on indication in high-volume laboratories, we offer a flow diagram (Figure ) that we believe allows for a streamlined approach for DIF case triaging by technical staff.We concur that educating submitting clinicians regarding DIF limitations in particular clinical settings (ie, connective tissue disease, porphyria, and LP), the need for DIF biopsies to be submitted with a biopsy for HE, and improving clinicianpathologist communication are key areas that will reduce the need for the full antibody panel, followed by a reduction in unnecessary DIF biopsies.Given the ever ballooning cost of health care in the US, it is imperative that the medical community choose wisely when spending health care dollars.The authors point out a key illustration of this when they suggest that we overestimated cost savings of DIF customization "because many laboratories no longer test albumin in their DIF panels."While some laboratories have voluntarily discontinued use of albumin, others have not, justifying its inclusion in our cost analysis.Spotlighting an area of pathology in which tradition plays a substantial role in why we still do what we do is necessary to achieve these changes.We believe that our proposed streamlining of the DIF protocol is an apt example of choosing wisely that should be done now rather than waiting until we exist in a perfectly optimized state of clinicianpathologist communication.
Abstract IA001: Harnessing evolutionary dynamics for control and cure of metastatic cancers
Authors: Robert Gatenby
Journal: Cancer Research (2022)

Abstract Although most metastatic cancers now have at least one effective therapy, evolution of resistance almost invariably leads to treatment failure and patient death. While often viewed as the result of a “resistance mutation,” many cancer cell resistance strategies simply involve increased expression of genes (e.g., xenobiotic metabolism) already in the human genome. Furthermore, clinical treatments to block the resistance mechanism (e.g. the MDR proteins) have generally been unsuccessful reflecting the multiplicity of available strategies. In an evolutionary context, however, the mere presence of a resistant phenotype is not sufficient for treatment failure. Rather, tumor progression requires proliferation of the resistant phenotype at a rate sufficient to produce the billions of cells necessary for clinically evident progressive disease. Importantly, the necessary molecular, cellular, and population dynamics necessary for cancer progression during treatment are deeply connected because there are often significant phenotypic costs from synthesis, maintenance, and operation of the molecular machinery of resistance that can reduce cellular proliferation and invasion particularly in the substrate-poor environment often present in clinical cancers. Evolution-based cancer treatment assumes that resistant phenotypes are invariably present prior to initiation of therapy and seeks to exploit evolutionary dynamics to delay or prevent proliferation of these cells. A specific example of this approach is adaptive therapy which is used in clinical settings in which cure is not achievable. Similar to widely accepted practices in pest management, adaptive therapy reduces or periodically withdraws treatment to maintain a stable population of treatment-sensitive cells that can use their fitness advantage (i.e. absence of the cost of resistance) to suppress proliferation of resistant phenotypes. This approach has been investigated in both pre-clinical and clinical conditions. A clinical trial in metastatic castrate-resistant prostate cancer (mCRPC) has been completed and will be discussed. Finally, when cure from a cancer treatment is possible but rare, evolutionary dynamics, based on observations in Anthropocene extinctions, can theoretically be used to increase the probability of complete eradication of the malignant population. Citation Format: Robert Gatenby. Harnessing evolutionary dynamics for control and cure of metastatic cancers [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr IA001.
Indoleamine 2,3-Dioxygenase 1 Deletion–Mediated Kynurenine Insufficiency in Vascular Smooth Muscle Cells Exacerbates Arterial Calcification
Authors: Liu Ouyang, Changjiang Yu, Zhiyong Xie, Xiaoyan Su, Zengmei Xu, Ping Song, Jian Li, Hui Huang, Ye Ding, Ming-Hui Zou
Journal: Circulation (2022)

IDO1 (indoleamine 2,3-dioxygenase 1) is the rate-limiting enzyme for tryptophan metabolism. IDO1 malfunction is involved in the pathogenesis of atherosclerosis. Vascular smooth muscle cells (VSMCs) with an osteogenic phenotype promote calcification and features of plaque instability. However, it remains unclear whether aberrant IDO1-regulated tryptophan metabolism causes VSMCs osteogenic reprogramming and calcification.
BMP signaling in the intestinal epithelium drives a critical feedback loop to restrain IL-13–driven tuft cell hyperplasia
Authors: Håvard T. Lindholm, Naveen Parmar, Claire Drurey, Marta Campillo Poveda, Pia M. Vornewald, Jenny Ostrop, Alberto Díez-Sanchez, Rick M. Maizels, Menno J. Oudhoff
Journal: Science Immunology (2022)

The intestinal tract is a common site for various types of infections including viruses, bacteria, and helminths, each requiring specific modes of immune defense. The intestinal epithelium has a pivotal role in both immune initiation and effector stages, which are coordinated by lymphocyte cytokines such as IFNγ, IL-13, and IL-22. Here, we studied intestinal epithelial immune responses using organoid image analysis based on a convolutional neural network, transcriptomic analysis, and in vivo infection models. We found that IL-13 and IL-22 both induce genes associated with goblet cells, but the resulting goblet cell phenotypes are dichotomous. Moreover, only IL-13-driven goblet cells are associated with classical NOTCH signaling. We further showed that IL-13 induces the bone morphogenetic protein (BMP) pathway, which acts in a negative feedback loop on immune type 2-driven tuft cell hyperplasia. This is associated with inhibiting
Safety and immunogenicity of the Rotavac and Rotasiil rotavirus vaccines administered in an interchangeable dosing schedule among healthy Indian infants: a multicentre, open-label, randomised, controlled, phase 4, non-inferiority trial
Authors: Suman Kanungo, Pranab Chatterjee, Ashish Bavdekar, Manoj Murhekar, Sudhir Babji, Richa Garg, Sandip Samanta, Ranjan K Nandy, Anand Kawade, Kangusamy Boopathi, Kaliaperumal Kanagasabai, Vineet Kumar Kamal, Velusamy Saravana Kumar, Nivedita Gupta, Shanta Dutta
Journal: The Lancet Infectious Diseases (2022)
A commentary on “Postoperative hiatal herniation after open vs. minimally invasive esophagectomy; a systematic review and meta-analysis” (Int J Surg 2021;93:106046). Paraconduit hiatal hernia: A relevant complication after radical esophagectomy with reconstruction via gastric pull-up. Suggestions for prevention
Authors: U.K. Fetzner, P.P. Grimminger
Journal: International Journal of Surgery (2022)
Transforming or tinkering: the world remains unprepared for the next pandemic threat
Authors: Helen Clark, Mauricio Cárdenas, Mark Dybul, Michel Kazatchkine, Joanne Liu, David Miliband, Anders Nordström, Preeti Sudan, Ernesto Zedillo, Thoraya Obaid, Rosemary McCarney, Elizabeth Radin, Mike Kalmus Eliasz, Christine McNab, Helena Legido-Quigley, Ellen Johnson Sirleaf
Journal: The Lancet (2022)
Arterial Ultrasound Testing to Predict Atherosclerotic Cardiovascular Events
Authors: Andrew N. Nicolaides, Andrie G. Panayiotou, Maura Griffin, Theodosis Tyllis, Dawn Bond, Niki Georgiou, Efthyvoulos Kyriacou, Costantinos Avraamides, Richard M. Martin
Journal: Journal of the American College of Cardiology (2022)
Improving the Hemocompatibility of Antimicrobial Peptidomimetics through Amphiphilicity Masking Using a Secondary Amphiphilic Polymer
Authors: Xianhui Chen, Cailing Zhou, Jianxue Wang, Tong Wu, E Lei, Yi Wang, Guopu Huang, Yue Yu, Qingyun Cai, Huangsheng Pu, Xinxin Feng, Yugang Bai
Journal: Advanced Healthcare Materials (2022)

Abstract Antimicrobial peptidomimetics (AMPMs) have received widespread attention as potentially powerful weapons against antibiotic resistance. However, AMPMs’ membrane disruption mechanism not only brings resistance‐resistant nature, but also nonspecific binding and disruption toward eukaryotic cell membranes, and consequently, their hemolytic activity is the primary concern on clinical applications. Here, the preparation and screening of an AMPM library is reported, through which a best‐performing hit, PT‐b1 , can be obtained. To further improve PT‐b1 ’s hemocompatibility, a strategy is devised to mask the amphiphilicity of the AMPM using a charge‐free, FDA‐approved amphiphilic polymer, Pluronic F‐127 (PF127). A PF127 solution containing PT‐b1 can form a temperature‐sensitive, absorbable hydrogel at higher concentration, but dissolve and complex with PT‐b1 through hydrophobic interactions at lower concentration or lower temperature. The complexation from PF127 can mask the amphiphilicity of PT‐b1 and render it extremely hemocompatible, yet the reversibility in such nanocomplexation and the existence of a secondary mechanism of action ensure that the AMPM's potency remains unchanged. The in vivo effectiveness of this antimicrobial hydrogel system is demonstrated using a mice wound infection model established with Methicillin‐resistant Staphylococcus aureus , and observations indicate the hydrogel can promote wound healing and suppress bacteria‐caused inflammation even when resistant pathogens are involved.
Underwater endoloop-assisted endoscopic resection for colorectal pedunculated polyps
Authors: Shunsuke Yamamoto, Adolfo Parra-Blanco
Journal: Endoscopy (2022)

Detachable snares, such as endoloops, are effective for the removal of pedunculated colorectal polyps; however, they are often difficult to apply [1] [2] [3]. The underwater method and related techniques using instruments with waterjet functions are increasingly being developed and applied for the resection of colonic polyps [4] [5]. Here, we demonstrate the use of the underwater method to facilitate endoloop-assisted polypectomy in four patients with pedunculated colonic polyps ([Video 1]).
Rabies in a Dog Imported from Azerbaijan — Pennsylvania, 2021
Authors: Florence Whitehill, Sarah Bonaparte, Claire Hartloge, Lauren Greenberg, Panayampalli S. Satheshkumar, Lillian Orciari, Michael Niezgoda, Pamela A. Yager, Emily G. Pieracci, Jacquelyn McCullough, Anders Evenson, Clive M. Brown, Hannah Schnitzler, Beth Lipton, Kimberly Signs, Mary Grace Stobierski, Connie Austin, Staci Slager, Mark Ernst, Janna Kerins, Aliza Simeone, Amber Singh, Shelby Hale, Danielle Stanek, Patrick Shehee, Sally Slavinski, Darby McDermott, Patricia A. Zinna, Rebecca Campagna, Ryan M. Wallace
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

On June 16, 2021, rabies virus infection was confirmed in a dog included in a shipment of rescue animals imported into the United States from Azerbaijan. A multistate investigation was conducted to prevent secondary rabies cases, avoid reintroduction of a dog-maintained rabies virus variant (DMRVV), identify persons who might have been exposed and would be recommended to receive rabies postexposure prophylaxis, and investigate the cause of importation control failures. Results of a prospective serologic monitoring (PSM) protocol suggested that seven of 32 (22%) animals from the same shipment as the dog with confirmed rabies virus infection and who had available titer results after rabies vaccine booster had not been adequately vaccinated against rabies before importation. A requirement for rabies vaccination certificates alone will not adequately identify improper vaccination practices or fraudulent paperwork and are insufficient as a stand-alone rabies importation prevention measure. Serologic titers before importation would mitigate the risk for importing DMRVV.
SVA Retrotransposons and a Low Copy Repeat in Humans and Great Apes: A Mobile Connection
Authors: Annette Damert
Journal: Molecular Biology and Evolution (2022)

Abstract Segmental duplications (SDs) constitute a considerable fraction of primate genomes. They contribute to genetic variation and provide raw material for evolution. Groups of SDs are characterized by the presence of shared core duplicons. One of these core duplicons, low copy repeat (lcr)16a, has been shown to be particularly active in the propagation of interspersed SDs in primates. The underlying mechanisms are, however, only partially understood. Alu short interspersed elements (SINEs) are frequently found at breakpoints and have been implicated in the expansion of SDs. Detailed analysis of lcr16a-containing SDs shows that the hominid-specific SVA (SINE-R-VNTR-Alu) retrotransposon is an integral component of the core duplicon in Asian and African great apes. In orang-utan, it provides breakpoints and contributes to both interchromosomal and intrachromosomal lcr16a mobility by inter-element recombination. Furthermore, the data suggest that in hominines (human, chimpanzee, gorilla) SVA recombination-mediated integration of a circular intermediate is the founding event of a lineage-specific lcr16a expansion. One of the hominine lcr16a copies displays large flanking direct repeats, a structural feature shared by other SDs in the human genome. Taken together, the results obtained extend the range of SVAs’ contribution to genome evolution from RNA-mediated transduction to DNA-based recombination. In addition, they provide further support for a role of circular intermediates in SD mobilization.
Reporting guideline for the early-stage clinical evaluation of decision support systems driven by artificial intelligence: DECIDE-AI
Authors: Baptiste Vasey, Myura Nagendran, Bruce Campbell, David A. Clifton, Gary S. Collins, Spiros Denaxas, Alastair K. Denniston, Livia Faes, Bart Geerts, Mudathir Ibrahim, Xiaoxuan Liu, Bilal A. Mateen, Piyush Mathur, Melissa D. McCradden, Lauren Morgan, Johan Ordish, Campbell Rogers, Suchi Saria, Daniel S. W. Ting, Peter Watkinson, Wim Weber, Peter Wheatstone, Peter McCulloch, Aaron Y. Lee, Alan G. Fraser, Ali Connell, Alykhan Vira, Andre Esteva, Andrew D. Althouse, Andrew L. Beam, Anne de Hond, Anne-Laure Boulesteix, Anthony Bradlow, Ari Ercole, Arsenio Paez, Athanasios Tsanas, Barry Kirby, Ben Glocker, Carmelo Velardo, Chang Min Park, Charisma Hehakaya, Chris Baber, Chris Paton, Christian Johner, Christopher J. Kelly, Christopher J. Vincent, Christopher Yau, Clare McGenity, Constantine Gatsonis, Corinne Faivre-Finn, Crispin Simon, Danielle Sent, Danilo Bzdok, Darren Treanor, David C. Wong, David F. Steiner, David Higgins, Dawn Benson, Declan P. O’Regan, Dinesh V. Gunasekaran, Dominic Danks, Emanuele Neri, Evangelia Kyrimi, Falk Schwendicke, Farah Magrabi, Frances Ives, Frank E. Rademakers, George E. Fowler, Giuseppe Frau, H. D. Jeffry Hogg, Hani J. Marcus, Heang-Ping Chan, Henry Xiang, Hugh F. McIntyre, Hugh Harvey, Hyungjin Kim, Ibrahim Habli, James C. Fackler, James Shaw, Janet Higham, Jared M. Wohlgemut, Jaron Chong, Jean-Emmanuel Bibault, Jérémie F. Cohen, Jesper Kers, Jessica Morley, Joachim Krois, Joao Monteiro, Joel Horovitz, John Fletcher, Jonathan Taylor, Jung Hyun Yoon, Karandeep Singh, Karel G. M. Moons, Kassandra Karpathakis, Ken Catchpole, Kerenza Hood, Konstantinos Balaskas, Konstantinos Kamnitsas, Laura Militello, Laure Wynants, Lauren Oakden-Rayner, Laurence B. Lovat, Luc J. M. Smits, Ludwig C. Hinske, M. Khair ElZarrad, Maarten van Smeden, Mara Giavina-Bianchi, Mark Daley, Mark P. Sendak, Mark Sujan, Maroeska Rovers, Matthew DeCamp, Matthew Woodward, Matthieu Komorowski, Max Marsden, Maxine Mackintosh, Michael D. Abramoff, Miguel Ángel Armengol de la Hoz, Neale Hambidge, Neil Daly, Niels Peek, Oliver Redfern, Omer F. Ahmad, Patrick M. Bossuyt, Pearse A. Keane, Pedro N. P. Ferreira, Petra Schnell-Inderst, Pietro Mascagni, Prokar Dasgupta, Pujun Guan, Rachel Barnett, Rawen Kader, Reena Chopra, Ritse M. Mann, Rupa Sarkar, Saana M. Mäenpää, Samuel G. Finlayson, Sarah Vollam, Sebastian J. Vollmer, Seong Ho Park, Shakir Laher, Shalmali Joshi, Siri L. van der Meijden, Susan C. Shelmerdine, Tien-En Tan, Tom J. W. Stocker, Valentina Giannini, Vince I. Madai, Virginia Newcombe, Wei Yan Ng, Wendy A. Rogers, William Ogallo, Yoonyoung Park, Zane B. Perkins
Journal: Nature Medicine (2022)
Detection of Occult Recurrence Using Circulating Tumor Tissue Modified Viral HPV DNA among Patients Treated for HPV-Driven Oropharyngeal Carcinoma
Authors: Barry M. Berger, Glenn J. Hanna, Marshall R. Posner, Eric M. Genden, Julio Lautersztain, Stephen P. Naber, Catherine Del Vecchio Fitz, Charlotte Kuperwasser
Journal: Clinical Cancer Research (2022)

Despite generally favorable outcomes, 15% to 25% of patients with human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) will have recurrence. Current posttreatment surveillance practices rely on physical examinations and imaging and are inconsistently applied. We assessed circulating tumor tissue modified viral (TTMV)-HPV DNA obtained during routine posttreatment surveillance among a large population of real-world patients.This retrospective clinical case series included 1,076 consecutive patients across 108 U.S. sites who were ≥ 3 months posttreatment for HPV-driven OPSCC and who had one or more TTMV-HPV DNA tests (NavDx, Naveris Laboratories) obtained during surveillance between February 6, 2020, and June 29, 2021. Test results were compared with subsequent clinical evaluations.Circulating TTMV-HPV DNA was positive in 80 of 1,076 (7.4%) patients, with follow-up available on all. At first positive surveillance testing, 21 of 80 (26%) patients had known recurrence while 59 of 80 (74%) patients were not known to have recurrent disease. Among these 59 patients, 55 (93%) subsequently had a confirmed recurrence, 2 patients had clinically suspicious lesions, and 2 had clinically "no evidence of disease" (NED) at last follow-up. To date, the overall positive predictive value of TTMV-HPV DNA testing for recurrent disease is 95% (N = 76/80). In addition, the point-in-time negative predictive value is 95% (N = 1,198/1,256).These findings highlight the clinical potential for circulating TTMV-HPV DNA testing in routine practice. As a surveillance tool, TTMV-HPV DNA positivity was the first indication of recurrence in the majority of cases, pre-dating identification by routine clinical and imaging exams. These data may inform future clinical and guideline-endorsed strategies for HPV-driven malignancy surveillance. See related commentary by Colevas, p. 4171.
Impact of Sex and Gender on Autoimmune Lung Disease: Opportunities for Future Research: NHLBI Working Group Report
Authors: Elizabeth R. Volkmann, Jill Siegfried, Tim Lahm, Corey E. Ventetuolo, Stephen C. Mathai, Virginia Steen, Erica L. Herzog, Rebecca Shansky, Montserrat C. Anguera, Sonye K. Danoff, Jon T. Giles, Yvonne C. Lee, Wonder Drake, Lisa A. Maier, Marrah Lachowicz-Scroggins, Heiyoung Park, Koyeli Banerjee, Josh Fessel, Lora Reineck, Louis Vuga, Elliott Crouser, Carol Feghali-Bostwick
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"Impact of Sex and Gender on Autoimmune Lung Disease: Opportunities for Future Research: NHLBI Working Group Report." American Journal of Respiratory and Critical Care Medicine, 206(7), pp. 817–823